Human neutrophil peptides 1-3 protect the murine urinary tract from uropathogenic Escherichia coli challenge
Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 (DEFA1A3) are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the DEFA1A3 locus are associated with UTI and pyelonephritis risk. Because DEFA1A3 is not expressed in mice, we utilized human DEFA1A3 gene transgenic mice (DEFA4/4) to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic Escherichia coli (UPEC) stimulus in vitro and in vivo. We also demonstrate transgenic human DEFA4/4 gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the DEFA1A3 locus and alpha-defensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 119(2022), 40 vom: 04. Okt., Seite e2206515119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Canas, Jorge J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.09.2022 Date Revised 04.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2206515119 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346781426 |
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| 100 | 1 | |a Canas, Jorge J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human neutrophil peptides 1-3 protect the murine urinary tract from uropathogenic Escherichia coli challenge |
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| 500 | |a Date Revised 04.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 (DEFA1A3) are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the DEFA1A3 locus are associated with UTI and pyelonephritis risk. Because DEFA1A3 is not expressed in mice, we utilized human DEFA1A3 gene transgenic mice (DEFA4/4) to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic Escherichia coli (UPEC) stimulus in vitro and in vivo. We also demonstrate transgenic human DEFA4/4 gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the DEFA1A3 locus and alpha-defensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a antimicrobial peptides | |
| 650 | 4 | |a collecting ducts | |
| 650 | 4 | |a molecular biology | |
| 650 | 4 | |a pyelonephritis | |
| 650 | 4 | |a transgenic mouse | |
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| 650 | 7 | |a human neutrophil peptide 2 |2 NLM | |
| 650 | 7 | |a human neutrophil peptide 3 |2 NLM | |
| 700 | 1 | |a Liang, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Saxena, Vijay |e verfasserin |4 aut | |
| 700 | 1 | |a Hooks, Jenaya |e verfasserin |4 aut | |
| 700 | 1 | |a Arregui, Samuel W |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Hongyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yunlong |e verfasserin |4 aut | |
| 700 | 1 | |a Kish, Danielle |e verfasserin |4 aut | |
| 700 | 1 | |a Linn, Sarah C |e verfasserin |4 aut | |
| 700 | 1 | |a Bdeir, Khalil |e verfasserin |4 aut | |
| 700 | 1 | |a Cines, Douglas B |e verfasserin |4 aut | |
| 700 | 1 | |a Fairchild, Robert L |e verfasserin |4 aut | |
| 700 | 1 | |a Spencer, John D |e verfasserin |4 aut | |
| 700 | 1 | |a Schwaderer, Andrew L |e verfasserin |4 aut | |
| 700 | 1 | |a Hains, David S |e verfasserin |4 aut | |
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